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Biomedical subjects

K M Edwards

Publications and source records attributed to K M Edwards.

At least 145 records · Page 8Linked to original sources

Intrahepatic cholangitis associated with mucocutaneous lymph node syndrome.

Although gallbladder hydrops occurs frequently in patients with mucocutaneous lymph node syndrome (MCLS), the etiology of the gallbladder lesion is unclear. Recently we performed a liver biopsy on a child with severe MCLS and demonstrated selective invasion of biliary ductular epithelial cells by polymorphonuclear leukocytes with sparing of the hepatocytes. The possible role of the selective destruction of biliary cells in the pathogenesis of biliary disease in MCLS is discussed.

Cholangitis↗

Clinical features of mild systemic meningococcal disease with characterization of bacterial isolates.

Neisseria meningitidis is an important cause of fulminant septicemia and meningitis in children. Only limited reports of mild disease associated with this organism exist. In this study, we describe eight children, ages 2.5-19 months, with mild meningococcal disease and characterize the meningococcal isolates from some of these patients. Children with mild meningococcal disease presented with a mean fever of 40.1 degrees C, but without purpura or petechiae. Five were diagnosed as having otitis media and were not thought to be seriously ill when initially observed. Six of the eight children had complete resolution of their clinical symptoms as outpatients. One had apparent meningococcal meningitis that sterilized without antibiotic therapy, and one had persistent low grade bacteremia that cleared within 48 hours after institution of parenteral antibiotics. Characterization of the meningococcal isolates from three of the patients revealed that the organisms were encapsulated, piliated, and contained similar outer membrane proteins. This report confirms that blood stream invasion by N. meningitidis organisms may result in clinically mild disease.

Blood Bactericidal Activity↗

Adenovirus infections in young children.

The importance of adenovirus in initiating respiratory disease in young children is stressed in this report. The incidence, clinical illness, asymptomatic carriage, and serologic response of acute adenovirus-associated infection are described in a carefully followed cohort of normal children cultured with each episode of febrile respiratory illness. During a 6-year period, 8.2% of 1,416 nasal washings obtained from sick infants and children less than 7 years of age yielded adenovirus. Adenoviruses were isolated from only 1/174 (0.6%) cultures taken from well children. Typing of 98 isolates showed 81% to be types 1 or 2. A greater than or equal to fourfold rise in neutralizing titer was seen in 45/59 (76%) sampled. In a subset of the cohort observed for 2-week periods in a day care setting, 14 of 21 well children (67%) exposed to symptomatic children with adenovirus infection developed febrile respiratory symptoms and shedding of the same serotype within 2 weeks of exposure. This study confirms that adenovirus has a high attack rate and causes significant respiratory disease in young children.

Adenoviridae Infections↗

Ophthalmomyiasis interna causing visual loss.

Ophthalmomyiasis interna caused severe intraocular inflammation and loss of vision in two eyes. In the first eye, the organism was found in the vitreous and created a severe uveitis; a second-stage larva of Hypoderma lineatum was later removed from the anterior chamber. Phthisis bulbi ensued with loss of all vision. In a second eye, a subretinal maggot was observed to produce tracks in the pigment epithelium, with subretinal and vitreous hemorrhage. Severe uveitis and traction retinal detachment later developed. Despite successful reattachment of the retina, visual acuity remained only light perception. These cases demonstrate that ophthalmomyiasis interna is not always a benign condition.

Blindness↗

Binding of C-reactive protein to the pneumococcal capsule or cell wall results in differential localization of C3 and stimulation of phagocytosis.

C-reactive protein (CRP) is a serum protein that shows rapid increases of as much as 1000-fold in concentration in response to infection, traumatic injury, or inflammation. CRP reacts with the phosphocholine moiety of pneumococcal cell wall C-polysaccharide, and this reaction can lead to complement activation in vitro and protection against pneumococcal infection in vivo. We have previously studied the chemiluminescence response of human neutrophils to Streptococcus pneumoniae as a measure of in vitro opsonophagocytosis by CRP and complement. CRP in the presence of complement was an effective opsonin for S. pneumoniae serotype 27 (Pn27), but not for serotypes 3 or 6. Because Pn27 differs from most serotypes of S. pneumoniae in containing phosphocholine in its capsular polysaccharide, we have determined the sites of CRP and C3 fixation to Pn27 and S. pneumoniae serotype 4 (Pn4), and related these to the ability of CRP and complement to opsonize these serotypes in vitro. By using a chemiluminescence (CL) assay to measure opsonophagocytosis, CRP was shown to enhance the response of human neutrophils and monocytes to Pn27 in the presence of normal human serum. The CL response of neutrophils and monocytes to Pn4 was not affected by the addition of CRP to serum. The addition of anti-capsular antibody to Pn4 and Pn27 enhanced the CL responses of both neutrophils and monocytes to both bacteria. The localization of bound CRP and C3 on Pn4 and Pn27 was determined by immunoelectron microscopy. CRP bound to Pn4 only in the cell wall region and C3 was located in this area whether or not CRP was present. Anti-capsular antibody deposited C3 in the capsule of Pn4. In contrast, Pn27 bound CRP throughout the capsule and cell wall areas. C3 was deposited in the cell wall region of Pn27 by serum alone and in the cell wall region and capsule when CRP or anti-capsular antibody was present. Because C3 fixation to the capsule was consistently associated with enhanced responses by phagocytic cells, it appears that the site of CRP binding and subsequent complement activation may be critical in the opsonophagocytosis of S. pneumoniae. These findings extend the correlation between capsular C3 and opsonization to a nonimmune system. By using CRP and different pneumococcal serotypes we have shown that the same molecules that are effective in the stimulation of phagocytic cells when bound to the capsule are not effective when bound to the cell wall.

Animals↗

Pneumococcal vaccine in normal children. Primary and secondary vaccination.

A pneumococcal polysaccharide vaccine containing 50 micrograms of each of 14 pneumococcal types was administered to 79 children 2 to 5 years of age. In earlier studies, 52 of these children had received pneumococcal vaccine; 27 had received a placebo. Local reactions were significantly greater in the reimmunized group. Antibody response to the vaccine was similar in both groups. Mean fold rises to most vaccine components were at least twofold. The response to specific pneumococcal types was unrelated to the frequency with which each type causes illness. Response to type 6 continued to be poor for children up to age 5 years. A vaccine with improved immunogenicity must be developed before widespread use in normal children is advocated. However, the 14-valent pneumococcal polysaccharide vaccine currently available is moderately immunogenic in children by age 2 years and should be given to patients with increased risk of pneumococcal illness at that time.

Age Factors↗

Antibody and complement in the stimulation of neutrophil chemiluminescence by Neisseria meningitidis: studies in a patient with complete deficiency of C7.

When an eight-year-old boy with a syndrome compatible with disseminated neisseria infection was found to lack C7, studies on the role of antibody and complement in the interaction of polymorphonuclear leukocytes (PMNLs) and Neisseria were initiated with use of a luminol-enhanced chemiluminescence assay. The chemiluminescent response to opsonized Neisseria meningitidis was markedly lower than the response to opsonized zymosan or Streptococcus pneumoniae but was similar to that obtained with Haemophilus influenzae type b. IgG antibody to N. meningitidis was shown to enhance the chemiluminescent response. The chemiluminescent response of PMNLs to N. meningitidis was normal when the bacteria were incubated with sera deficient in C5, C6, or C7 but was absent in serum lacking C2. Thus, both antibody and the early-acting proteins of the classical complement pathway appear to be essential for maximal stimulation of PMNL oxidative metabolism by N. meningitidis, although the late-acting components of complement are not.

Animals↗

C-reactive protein reactivity with complement and effects on phagocytosis.

In the studies described here we have attempted to evaluate the hypothesis that CRP may function in host defense using two systems in which CRP in the presence of C appears to have opsonic properties. In the first, CRP and C were found to stimulate ingestion of erythrocytes by human monocyte or mouse macrophages in vitro, and to alter clearance patterns in vivo. In the second, we have studied opsonization of S. pneumoniae by CRP and C. Experiments with human neutrophils indicate that although CRP and C can enhance opsonization of S. pneumoniae, this effect is more pronounced in the absence of antibody. In vivo CRP was found to protect mice against intravenous infection with S. pneumoniae.

Animals↗

Effect of C-reactive protein on the complement-mediated stimulated of human neutrophils by Streptococcus pneumoniae serotypes 3 and 6.

C-reactive protein (CRP) has long been known to appear in the sera of individuals with inflammatory processes, but its role in host defense against bacterial infection is unclear. We have recently demonstrated that CRP in the presence of the classical complement pathway markedly enhances the opsonization of Streptococcus pneumoniae serotype 27 by polymorphonuclear leukocytes (Edwards et al., J. Immunol. 128:2493-2496). In this report we have extended these studies to characterize the role of CRP in the opsonization of other S. pneumoniae serotypes. Two clinically important serotypes, 3 and 6, were tested along with the nonpathogenic rough strain R36a. All strains were found to bind radiolabeled CRP in the presence of calcium and to activate the classical complement pathway in normal human serum. However, the opsonophagocytic response of polymorphonuclear leukocytes to the strains, measured by chemiluminescence, was quite different. In contrast to the marked enhancement by CRP of the chemiluminescent response to serotype 27 in normal human serum, CRP had no effect on the opsonization of serotype 6 or R36a and inhibited opsonization of serotype 3 in normal serum. In serum from a hypogammaglobulinemic patient, CRP enhanced the lowered chemiluminescent response to serotype 3 and 6 organisms but did not restore the response to normal. The greater opsonic effect of CRP on serotype 27 may be related to the ability of CRP to bind to the capsule as well as to the cell wall of this serotype or to differences in the amount of CRP bound to the different strains.

C-Reactive Protein↗

A role for C-reactive protein in the complement-mediated stimulation of human neutrophils by type 27 Streptococcus pneumoniae.

Although C-reactive protein (CRP) has been shown to be opsonic when bound to erythrocytes, its role in bacterial phagocytosis is unclear. Chemiluminescence (CL), a measure of the metabolic stimulation of neutrophils, was used to investigate the effects of CRP and complement (C) on the interaction between phagocytes and Streptococcus pneumoniae, type 27 (Pn27). CRP binding to Pn27 was demonstrated by using radiolabeled CRP, and Scatchard analysis indicated a saturation binding of about 10(7) CRP molecules/CFU. When Pn27 was pretreated with normal human serum and added to neutrophils, the CL response observed was directly related to the number of bacteria and the amount of serum added. Although bacteria pretreated with CRP alone produced minimal CL, the addition of CRP to serum resulted in a two to 13-fold enhancement of the CL response. CRP enhancement of CL was not observed with heated serum or serum from a patient genetically lacking C2. CRP bound to Pn27 was found to cause consumption of C3 and C4 in normal human serum, indicating activation of the classical C pathway. Because CRP opsonization might provide early protection in the nonimmune host, we tested the ability of CRP to enhance opsonization in serum with markedly decreased immunoglobulin. CRP enhanced the CL response in serum from a hypogammaglobulinemic patient to between 12 and 16 times the serum control. These studies show CRP binds to Pn27 and in the presence of C enhances the opsonization of these organisms. These findings support the concept that CRP plays a protective role in bacterial infection.

Agammaglobulinemia↗

Multifocal osteomyelitis caused by Paecilomyces varioti in a patient with chronic granulomatous disease.

This report describes an 18-year-old male patient with chronic granulomatous disease who developed cutaneous nodules and multifocal osteomyelitis with the saprophytic fungus Paecilomyces varioti. After several biopsies the organism was identified. Anti-fungal susceptibility testing was performed. Combination therapy with amphotericin B and gamma-interferon followed by long-term therapy with itraconazole and gamma-interferon resulted in a clinical response.

Adolescent↗

Pediatric immunizations.

The record of disease prevention in children is an impressive testament to our universal immunization program. However, these successes are being threatened by rates of vaccination in some areas of the country that are substantially less than those seen in the developing world. Unless the pediatric immunization rates are improved, epidemics of other vaccine-preventable diseases will recur, as evidenced by the measles outbreaks. Although the tools needed for disease prevention are available, the means for their delivery are lacking. It is the obligation of us all to immunize the nation's children.

Bacterial Infections↗